Friday, March 31, 2017

March SciDay Friday!

Well, we're a quarter of the way through 2017 and what a year it's been for science so far! There have been some challenges, and even more challenges, and for a change of pace, more challenges. It's incredibly frustrating and the War on Science has only just begun. But today, let's primarily focus on some of the victories. I neglected to post a monthly update last month, so today's post will be a conglomeration of science published predominantly in February and March.

I'm also excited to announce that I'll be posting regular blog posts for the science fiction magazine Cosmic Roots and Eldritch Shores. Cosmic Roots is a new magazine featuring science fiction, fantasy, and other short stories. I'll be contributing as often as I can on fact-based articles about science and society. I'll be sure to link my posts here as well, as many of the posts will be open access and free. Interviews and other types of articles I may write will be for subscribers to the magazine and if you like reading science fiction short stories it is worth getting a subscription.

Okay, so what's been happening in the world of science?

There has been considerable attention on the environment lately, which should come as no surprise given how important our climate is to our health and sustainability as a country and planet. Last month, researchers in Germany published a comprehensive report on oceanic oxygen content and reported a 2% global decline in oxygen levels in the ocean since at least the 1960's. The levels of decline were variable by region and depth and a handful of areas even saw an increase in oxygen content. This type of comprehensive assessment is very important given the link between ocean oxygen levels and aquamarine health. If oxygen levels in the deeper parts of the ocean continue to drop as projected, the reduction in diversity of life and resources provided by our oceans will greatly impact society.

For example, water oxygenation is important for plant life and coral reef health in coastal environments. Another recent study found that seagrasses in coastal regions can reduce pathogenic bacterial populations in coastal ocean waters that are harmful to humans and sea creatures, alike. This is important evidence that healthy seagrass meadows sustain a ecosystem that has direct benefit to human health along the coasts (where a majority of humans live) and this is linked to the oxygen levels in the oceans. This balance will be vital to study and protect.

Physics has also had some remarkable discoveries and advances. Of course, the 'big one' was the discovery of seven planets that orbit the dwarf star TRAPPIST-1. TRAPPIST-1 is roughly 40 light-years away, so we won't be heading over to check it out anytime soon. However, each planet is close enough to the dwarf star that it could be warm enough for liquid water, and perhaps even life. This is a monumental discovery, as there are now known and nearby solar systems that could be hospitable for humans or other forms of life. Identifying this system gives researchers the opportunity to study how solar systems like ours formed, the requirements for liquid water on planets orbiting stars that are different from the Sun, and if these planets have any atmospheric conditions that support life...perhaps even if they contain oxygen. It's time to fire up the generation ships.

On the other end of the physics spectrum, researchers in Vienna have provided the first proof-of-principle experiment that confirms important aspects of quantum entanglement. Okay, what the hell does that even mean? In a nutshell, quantum entanglement suggests that some information can indeed travel faster than the speed of light. If two particles of matter become 'entangled', no matter how far apart you separate them, whether it's across a town, or galaxy, or the universe...what you do to one particle will automatically influence what happens to the other particle, regardless of the distance between them. Is your mind blown yet?

It's a lot to take in and I'm admittedly not the best source of information on this. The Atlantic has a very good article about what entanglement really is, the importance of this breakthrough, and Einstein's thoughts on 'spooky action at a distance', as he called it. I suggest checking it out as it explains everything very well.

Switching gears over to biology, I found some interesting articles I thought were worth bringing to your attention. DNA Fountain was just announced, the most current platform available to store data and information in strands of DNA. DNA Fountain was able to perfectly record, code, and decode movies and digital files (up to 2.5 Mb) in strands of physical DNA. While the sizes of these files isn't really impressive, the scalability of the DNA Fountain is the innovation being reported, with a maximum potential of up to 680 petabytes of information stored using this method. To put that into perspective, some of the largest, commercially-available external hard drives can store about10 terabytes of a single gram of DNA could theoretically store 680,000x more information. Cost efficiency is a concern at this point, as is error-free recording, but the future of information storage may very well be using our own genetic code. Very cool.

Speaking of DNA, it's long been known that as we grow older we accumulate more DNA damage and mutations in our cells. DNA mutations can be caused by environmental exposures (such as UV radiation or from carcinogens found in cigarettes), errors in DNA replication when a cell divides, or even the stochastic process where some DNA nucleotides will spontaneously turn into another (this is called DNA deamination). In my opinion, the accumulation of DNA mutations can lead to predisposition to many diseases, but that can be hard to accurately assess. In fact, there is still an ongoing debate as to how much age-related mutations contribute to the onset of  diseases, like cancer. The latest paper by Bert Vogelstein at John Hopkins attempts to address that issue in cancer. His laboratory is reporting that of the three ways DNA mutations can lead to cancer (1. through inheritance; 2. via environmental exposure; or 3. errors in DNA replication during cell division), random errors in DNA replication explain nearly two-thirds of all cancers.

This is a very provocative paper and assuredly cancer researchers are going to go to battle over this data. If correct, it means that a majority of cancers are caused at random and may not be preventable...some researchers are simply calling it bad luck. This has implications for prevention and therapy and it does agree with the history of studying cancer, in that cancer is now seen as a complex variety of conditions dependent upon the type of mutation driving the cellular growth and the tissue of origin. This finding also means a lot of work is going to be needed in the future to make cancer prevention and treatment more personalized so that those who develop cancer survive and with as few side effects as possible.

The last paper I'll highlight is a study of predicted life-expectancy in 35 industrialized countries around the globe. No surprise, the United States is projected to have one of the lowest gains in life expectancy in the developed world. With some of the failures in the Affordable Care Act and the new Administration's growing War on Science, particulary the idiotic ambitions to drastically reduce the science and health research capacity in the United States, this issue will undoubtedly become more important and apparent in the coming years. The authors of the report put it best and I'll just place their comments right here:

"Notable among poor-performing countries is the USA, whose life expectancy at birth is already lower than most other high-income countries, and is projected to fall further behind such that its 2030 life expectancy at birth might be similar to the Czech Republic for men, and Croatia and Mexico for women. The USA has the highest child and maternal mortality, homicide rate, and body-mass index of any high-income country, and was the first of high-income countries to experience a halt or
possibly reversal of increase in height in adulthood, which is associated with higher longevity. The USA is also the only country in the OECD without universal health coverage, and has the largest share of unmet health-care needs due to financial costs. Not only does the USA have high and rising health inequalities, but also life expectancy has stagnated or even declined in some population subgroups. Therefore, the poor recent and projected US performance is at least partly due to high
and inequitable mortality from chronic diseases and violence, and insufficient and inequitable health care."

But the best strategy is definitely to reduce federal research support for these important issues...blah!

Other tidbits:

-Apparently there is going to be a big dustup in the dinosaur world. Last week a study in Nature was published that called for an entire reorganization of the classification and naming of Dinosaurs. Hopefully the Brontosaurus returns! If any dinosaurs feel chumped by how things shake out, they can certainly phone a friend in Pluto.

-Early in human history, some of our ancestors interbred with Neanderthals and remnants of the Neanderthal genome are found in certain human populations. This month another study was published that provides evidence that genetic elements humans inherited from Neanderthals are functional and contribute to human phenotype variation (not all humans have Neanderthal ancestry!).

So there you have it. Until next time, enjoy Spring!

Tuesday, February 14, 2017

Thoughts On My March for Science

Many scientists have already publicly announced their support for the March for Science that is going to take place on Earth Day, April 22nd, in Washington D.C. and across the nation and world. I've already declared my intentions to join in, but the more I've thought about why I'm marching, the more I've realized I want to explain myself to anyone with the care to read this. (I'm also well aware of the fact that is already almost cliche to be a scientist posting on a personal blog about why the March for Science is important. But alas, the opportunity to talk about science and the fact that scientists and science supporters are coming out from the woodwork to unify around the idea of a free and informed democracy is too good a chance to pass up!)

A few points I'd like to clarify before getting into the heart of this matter. First, not everyone agrees that there should be a march, while others have offered advice on how to make the most impact. Each of these articles discusses some very important points and in each case it's mentioned that there is a danger that this movement will become politicized and partisan and this will negatively affect the overall impact and message. This is very important and their advice and commentary should be heeded by everyone attending (and especially those who are organizing).

This event must not become a political partisan issue primarily because science in general is NOT a partisan issue. Science interacts with everyone in this nation, everyday. While my previous point may sound trite, it really is the core at which how our world works.

You can find a broad list of goals and messages about the March for Science on their website, so I'm not going to dive into them. I'll just say in general I agree with the over-arching summary and most of the organizers' points, though not necessarily the ordering of those points (which I am assuming is listed top-down for emphasis, and if they aren't in any particular order I really hope the organizers will make a point of that on their webpage). Several of my points certainly overlap with theirs on a variety of levels, but these are the ones that speak most to me as an individual.

So, personally, what am I NOT marching for?

I am NOT marching for increased funding for my salary, or anyone's salary in science.

I am NOT marching to convince anyone that science will solve all our problems as a country.

I am NOT marching to further divide our polarized country.

So, personally, what AM I marching for?

1. Continued access to, and increased awareness of, the scientific process, how that creates new information, and engagement with anyone on why that information is fundamental to a sustained democracy.

2. Increased awareness about what science can do for the public good and how that will benefit everyone in society, regardless of religion, race, socioeconomic status, political party, gender, and sexual background.

3. Convincing other scientists that communication is a skill that needs training and development, starting at the undergraduate level.

4. Shifting the paradigm away from the dichotomy of scientific thinking some scientists have that there are scientists and then there is the public.

As a government scientist I feel it is my duty to make sure that everyone I know is aware about these reasons and my thought process behind them. My research and job are funded by your tax dollars and you have a right to know why I am taking these issues seriously. Also, I have dedicated my life to trying to increase humanity's knowledge about the world, as well as educating the next generation of scientists on the best practices to answer more questions and further increase that knowledge. Those endeavors are at the core of who I am and drive me to both write this post and walk on the streets of Washington D.C. to discuss this with anyone who is willing to listen.

I'd like to take the rest of your time to highlight some important points about each of the ideas I just put forth:

I am NOT marching for increased funding for my salary, or anyone's salary in science. I have already marched four years ago advocating for an increase in NIH funding. I'm not interested in my own salary, but rather a general increase in financial support for more labs and more experiments to study medicine, space, technological innovation, materials science, basic biological and behavioral research, food science, climate research, geological work, and others. All of those areas provide a benefit that supports our economy, our position as a leader in the free world, and help better improve the lives, health, safety, and protection of all us in this country and beyond.

I am NOT marching to convince anyone that science will solve all our problems as a country. I will not go into much detail here other than to admit that science will not solve all our issues. Science is a process that often takes time to come to the right solution or answer. Sometimes in science, like in life, an answer just isn't possible. But research CAN increase our potential as a society to solve large and complex problems. Many who do not understand how the scientific process works use this as an example to try and undermine how important the scientific process is and why disagreements among scientists about particular issues are an important aspect of that process (perhaps I'll write on this later). Please don't let these individuals sway your views on what good science can do for the world.

I am NOT marching to further divide our polarized country. Science impacts all of us, whether you believe it or not, or whether you care or not. I think it really hurts the democracy of our nation if science becomes politicized across party lines. There are many individuals on both sides of the aisle that can and will try to polarize these issues. The basic issues of information exposure, truth about how the world works, and how we might be able to implement good policy from that information are fundamental issues both Democrats and Republicans support, have supported in the past, and will continue to support in the future.

I AM marching for...continued access to, and increased awareness of, the scientific process, how that creates new information, and engagement with anyone on why that information is fundamental to a sustained democracy. 

An informed democracy and Congress can make better decisions. This relates to predicting the next earthquake or drought; when and if a new virus will jump to the Americas; how we can engineer our aging infrastructure; what space medicine can tell us about our own health down on the ground...the list goes on. There is a process involved with studying and publicizing this information that I will try to discuss leading up to the march and after. This includes peer review, funding, communication, and other aspects of the research enterprise.

All of this is of course related to education and access to information. Currently there are a handful of bills working their way through Congress that will limit your tax-paid access to basic information that may contribute to your education in the future, understanding your impact on the environment and how we can respond to it, your cyber security protections as a patient, or even allowing politicians to influence how basic science research is performed. There are some great bills as well that should be celebrated, such as the REAL Space Act to send us back to the Moon. In an age of post-truth and disbelief in fact, the only way to increase our potential as a nation is to keep discussing what is really impacting our world and why that should matter.

I AM marching for...Increased awareness about what science can do for the public good and how that will benefit everyone in society, regardless of gender, religion, race, socioeconomic status, sexuality, or political party.

I don't think I'll explain this one too much as it seems self-evident. However, if you are interested in how we can use data to understand our world better and begin to address disparities in a meaningful way, I'll direct you to this intuitive and free program where you can explore the disparities in our world. Our country is full of diverse people and varied experience and that makes our country strong. However, it means populations can be marginalized, discriminated against, and ignored. Sometimes this is intentional and other times it's not. Generating new data about these issues in our own country will greatly increase our chances of solving public health and societal crises like gang and gun violence, epidemics, and basic access to clean water and safe food, education, and opportunity. Data can help play a role in helping those who need government and societal attention the most. This is a fundamental core value of our country and science is an ally to this endeavor.

I AM marching for...the need to convince other scientists that communication is a skill that needs training and development, starting at the undergraduate level.

This is more relevant to those in my profession. Scientists can be horrible communicators and educators and this has to be addressed if science is going to continue to move forward in a productive way in this country. New strategies are needed to enhance early-career scientist training on issues of data communication and discussion...both within the scientific community and outside of it. Thankfully, new initiatives by the NIH and elsewhere are looking to enhance this for graduate school training, but more work is needed and at younger ages. The idea of communicating our research effectively to 'non-scientists' is also aligned with my fourth goal....

I AM marching for...shifting the paradigm away from the dichotomy of scientific thinking some scientists have that there are scientists and then there is the public.

There are so many people in this country who are interested in science and looking to do more with it in their lives who are not scientists at all. Scientists can often come off as arrogant and unapproachable, I'm guilty of this at times, and this can be an impediment to very important conversations that need everyone in the country to weigh-in on. I'm marching to increase that conversation and eliminate the perception in the scientific world that our work can't be understood by everyone. This is wrong and unfortunate and with proper training every scientist can and should be able to explain their work to anyone. Breaking down this dichotomy can help with this process and make data more approachable.

So there it is. That's why on April 22nd you'll find me in Washington, D.C. I hope you come as well because this issue will impact everyone and will help shape our discussions moving forward.

Tuesday, January 31, 2017

January's SciDay!

I've got one day left to keep up my tradition of commenting on each month's scientific breakthroughs. Since I've been teaching all month for the Citizen Science Program at Bard College (an amazing experience by the way), I've had almost no time to catalog and write about some of this month's interesting research papers. So last night in a flurry of activity I found a few things of particular interest and which I'll quickly summarize below:

Last month I commented that some natural compounds had been found that inhibit the CRISPR/Cas9 immune system in some bacteria. This is of note because this may be a natural way to better control human genome editing initiatives using CRISPR technology. This month, researchers at the University of California in San Francisco have identified in the genomes of phages (viruses that infect and kill bacteria cells only) a new set of inhibitors that target the CRISPR/Cas9 system in the pathogenic bacteria that cause listeria. These newly identified inhibitors also prevent CRISPR from working properly in human cells, too. As an added bonus, the study of these new molecules may help researchers explore novel ways to kill bacteria that are resistant to antibiotics. I learned during my time teaching at Citizen Science that the use of phages was widespread during WWII in Russia and elsewhere in order to combat bacterial infections on the battlefield. Phages were used in lieu of antibiotics...which weren't always readily available. Dr. Paul Turner at Yale (who also spoke at Bard this month and got me thinking about this) studies the use of viruses as a way to combat bacterial infections, especially against antibiotic resistant bacteria. (*Check out this link if you want to know more about it!*)

In my mind it is conceivable to engineer new phage viruses, with the genes coding for CRISPR inhibitors genetically engineered into their genomes, to be used as a new generation of viral drugs targeting antibiotic resistant bacteria. These viruses would then be resistant to the defense system of those bacteria and may be better at killing them in humans with bacterial diseases. Lots to mull over, but I think this could be very promising and I'll keep an eye out for research about this (if it doesn't already exist).

Additionally, what's really exciting is that this week researchers in Israel identified a new communication system between phages that help the viruses decide, upon infection of a bacterial cell, if they will kill the bacteria fast or enter the bacterial genome and go into a quiet, inactive state (called lysogeny) and kill the bacteria later. This is an incredible discovery and indicates that viruses are yet again more complex than we thought and capable of very simple communication. It was found that the genomes of distinct viruses have unique genes that code for small peptides and these small peptides are the messengers in this communications system. Think of the peptides as little hormones that tell the viruses when and if to kill the bacteria cell immediately upon infection, or later.

This of course opens the door to looking for these types of messengers in viruses that infect humans, and if they are indeed present, this may open up an entirely new avenue to explore for anti-viral therapy to save human lives. Now, that's A LOT of if's, but I'm feeling positive today and I hope this becomes a major breakthrough in our understanding of viral infections.

Next month I'd like to discuss some new announcements in NASA's Twins Study results. This is a study that is comparing the genetics and physiology of two astronauts after one of them, Scott Kelly, spent almost a year in space while his identical twin brother, Mark, stayed back on Earth. Scientists and clinicians are trying to better understand how space affects the human body. It's awesome research, with some ethical considerations that I'll get into next month.

I'll leave you with this: The Art of Saving a Life. This is an initiative by the Bill and Melinda Gates Foundation that brought together artists, poets, writers, film makers, and others to promote vaccine awareness using art as a medium. There is some incredible and beautiful art on this website, including some very moving and powerful short films. I wanted to highlight this here as an example of how anyone can help promote the cause of science (not just scientists) as a tool to protect and help people, promote awareness on this issue and others, increase our knowledge of how the world works, and encourage and support informed government policy.

Until next time, Go Spurs!

Tuesday, January 24, 2017

My Belief in Science and Truth in the Era of Trump

It hurts my heart that the current administration is engaging in deceit, falsehoods, and inaccuracy…and it is not even a week into the current changes. I work for the United States government and already many like-minded individuals and scientists are under governmental restriction to remain silent about simple facts of our world. I am fortunate to remain mostly outside of those restrictions…at the moment.

This form of silencing is reminiscent of governments in countries that rule by fear, devalue free thinking, and fuel propaganda. As a scientist and employee of the National Institutes of Health, I feel it is my duty to provide the most accurate truth that is available in the effort to educate and protect those that rely on accurate health information and fact…particularly those groups that are underrepresented in science.

Perhaps I’m looking at the dark side of the moon; perhaps I am overreacting. Both are possible, I’ll admit. But I promise to myself and my family and friends and to everyone else that I will not allow myself to be subjected to falsehood and the belief that there are ‘alternative’ truths to basic facts and truth. I feel incredibly passionate about this and I will not be dissuaded from engaging anyone, on either side of the aisle, from a productive discussion about these principles so long as people are willing to acknowledge that there is a reality to our world that can be defined in a reasonable way. This is dramatic maybe, but I feel this is imperative to define for myself and those I know as our country moves forward.   

Friday, December 30, 2016

December's SciDay Friday!

It's the last Friday of December and that means one final chance to talk about some science from the month. I'm only going to highlight four papers today, mainly because I didn't prepare this month's post as much as I typically do. Damn you, cookie-induced comas. But if you want to read more about the science from all of 2016, check out this Nature News Feature highlighting ten scientists who were vital this year. Not to be outdone, Science News has a rundown of their own.

The first paper can be found in Science Translational Medicine and explains some of the coolest science being performed right now. Researchers in Boston have developed a personal cancer vaccine for patients who suffered from acute myeloid leukemia (AML). Leukemia cells were isolated from patients with AML and fused together with dendritic cells (a type of immune cell that creates antigens which help the immune system recognize the stuff that shouldn't be there, like viruses and other cancer cells). These hybrid cells, part cancer and part immune, were injected back into AML patients who were in remission after successful chemotherapy treatment. The idea is that these hybrids would teach the other immune cells in each patient how to recognize the antigens from their own cancer and help them root out any leukemia cells that survived chemotherapy...thereby preventing recurrence of their cancer. Twelve of the seventeen patients have remained relapse-free for over four and a half years! Although some patients did relapse after this therapy, the rate of success warrants a closer look at this approach as a means of combating relapse or even as an initial treatment of metastatic cancers. The technology will need to be refined but this proof of principle in actual cancer patients is an awesome development.

The next paper investigates how animals experience time and I have to say, it's about time I started talking about time considering this blog is called Ripples in Time. Researchers in Portugal used drugs and optogenetics to manipulate midbrain dopamine neurons in mice to identify changes in their perception of time. (Quick refresher: Dopamine is a neurotransmitter that is involved with reward and behavior [among other functions] and optogenetics is the manipulation of the function of cells in live animals using fiber optic cables and light.)

Researchers found that dopamine neurons in the midbrain are directly involved in judging periods of elapsed time, either when the neurons are stimulated to release dopamine or suppressed. Since neural circuits are way beyond my expertise, I'm going to quote the end of this article to get the point across. The writing in brackets are my own to help clarify:

"Situations in which DAergic [dopamine neuron] activity is elevated naturally, such as states of high approach motivation, response uncertainty, or cognitive engagement are associated with underestimation of time. Conversely, situations that decrease DAergic activity, such as when fearful or aversive stimuli are presented, are associated with overestimation of time. These observations, together with our data, suggest that flexibility in time estimation may confer an adaptive advantage on the individual." 

This is direct evidence that the neuronal activity of some of the dopamine neurons in animal brains directly affect how we experience the length of time of events. So when I went to see Star Wars Rogue One I didn't even notice the movie was over two hours long because I was so excited while watching...whereas when I vacuumed the house earlier this week it felt like it took forever because my 'cognitive engagement' was low. Our perception of time is directly related to how stimulated we feel. This is cool stuff and may suggest how different people experience the timing of the same events in different ways. The results of this study also implied that the changes in perceptions in time were altered on the scale of actual seconds. This got me thinking. Maybe it isn't the Force that gives Jedi their ultra-fast reflexives, just really efficient dopamine neurons. But I digress... 
The third paper is an oddball, which I've tried to incorporate into each of these posts. Scientists in Europe used satellite data to measure changes in land surface water over the entire globe between 1984 and 2015. The satellite imagery had a resolution of less than 100 feet, which is pretty incredible, and this a first of its kind survey. A few summarized points of the findings:

-Globally, land-surface water has increased almost 94,000 square kilometers (about the size of Lake Superior, according to the researchers)
-The addition of this surface water is evenly distributed among the continents and linked to locations with reservoir building, dam construction, and are perhaps even influenced by changing local climates
-Over 70% of surface water loss was concentrated in the Middle East and Central Asia and linked to drought, river diversion and other human activities

I wanted to highlight this paper for a variety of reasons. I agree with the authors that this type of open-source mapping of available water resources is essential for the sustainability of clean and available water in the future. I think it is also smart to recognize that water loss and gain is influenced by human activity, drought, and maybe even the changing global climate, and charting the areas where the greatest changes are occurring can help predict areas that will need help in the future. Imagine in thirty years if the Middle East and Central Asia lost almost all of their surface water and the problems that could pose socially and politically. 

My main problem with this paper is that the authors try to present this data and incorporate their own commentary on climate change. I think that climate change is inherently a major influencer of water availability in our would be foolish not to think so. But the presentation of this data, particularly in the abstract, was written in such a way to first highlight the loss of global surface water and gloss over the fact that surface water actually had a net gain. I felt it was poorly worded and emphasized the wrong aspects of the data - the most important findings being the location and availability of surface water and where in the world changes in local climates (droughts) and human activity (dams) play a major role in this critical resource's availability and its management. It's a small, nit-picky critique, but it rubbed me the wrong way.

Oh well.

The last paper focuses on CRISPR (again!). I've talked about this technology in my last few posts and I feel it is so important that everyone understands the implications that I'm going to close my 2016 discussion about this topic. This time I'd like to feature a paper that came out in Cell and identifies natural compounds that inhibit Cas9, the essential enzyme component in the CRISPR gene editing system. Remember, the CRISPR system is a type of naturally-occurring immune system for bacteria which is applied against invading viruses that infect those bacteria. Inside the CRISPR gene system for the bacteria Neisseria meningitidis, researchers found three genes that code for proteins that inhibit the activity of Cas9 and therefor the CRISPR system. Several genes, related in function, are also found in the genomes of bacteria-infecting viruses. Together, this means that viruses have evolved a way around the CRISPR system and now those genes are being shared (and evolving on their own) between bacterium. 

The great news is researchers now have a way of inhibiting the CRISPR gene editing tool in animal cells with a natural protein found in bacteria. These proteins can be used as a drug/brake-system to limit off-target effects of CRISPR usage, protect specific tissues from being edited, and a way to prevent unforeseen downstream complications that may arise when using the CRISPR system in humans. I've long been concerned with the lack of restraints on the usage of CRISPR technology but the discovery and use of these enzymes is a step in the right direction with respect to control and safety. 

Wooo hoo! #science.

So that wraps up 2016. When I'm finished with teaching in January I'll write a few detailed posts about some controversies in science...starting with the reproducibility crisis. Until then, I wish you all a very wonderful and happy New Year and a great 2017!

Thursday, December 1, 2016

November (Sci)Day....Friday?!...Nope, Thursday!

I like to think I'm an organized person but keeping track of commitments and dates on my calendar has always proved challenging for me. So that's why November's SciDay Friday post, meant to be on the last Friday of November, is now today on a Thursday in December. I blame the copious amounts of turkey, gravy, and cranberries I stuffed into my mouth last week. My stupor lasted until Sunday and I completely forgot last Friday was November's last. At least I'm only a calendar day late.....

So without further adieu, it's time we talk a little bit about the science that was published over the last month!

I've posted extensively now on CRISPR and gene editing, including what it is and the ethics behind this new technology. The field is moving so fast that every month there are dozens of new articles refining this technology and applying it in disease research. Much of what I have previously discussed are my fears about the misuse of gene editing, but today I'm going to highlight why this technology could revolutionize healthcare.

Back in the mid-2000's, scientists were trying to find a way to get around the ethical and social dilemmas of using embryonic stem cells in their research. In 2006, researchers in Japan led by Dr. Shinya Yamanaka, published a report  highlighting the discovery that fibroblasts (cells found in our connective tissues in the body) could be 'reprogrammed' back into an embryonic-like state. With a combination of viruses and specific proteins, adult cells in the body could be reprogrammed and then induced in cell culture to grow into almost any other cell type - just like embryonic stem cells!

This discovery sent shockwaves throughout the biomedical field. The reprogrammed cells, called induced pluripotent stem cells (iPS cells), quickly became the hottest technology and Dr. Yamanaka ended up winning the Nobel Prize in 2012. The use of this new capability was obvious right away in that gene editing in mammals was now a reality. In 2007, a great paper came out highlighting the medical capabilities of iPS cells Briefly, scientists took fibroblasts from mice with sickle cell anemia, reprogrammed those cells into hematopoietic stem cells (HSCs; these cells are the stem cells that live in our bone marrow and give rise to all of our blood cells), fixed the mutation in the beta-globin gene that causes sickle cell anemia, and then transplanted the corrected HSCs into mice via a bone marrow transplant. The new stem cells seeded the bone marrow and gave rise to normal blood cells - curing these mice of their disease. This was one of the first applications of targeted gene therapy as a way to cure a genetic disease.

However, the technology has its complications. Viruses are required for the reprogramming and could be dangerous if used in humans, it's a difficult and expensive procedure, and it's not always successful. CRISPR technology can be the next generation of this approach because it's cheaper to use, more precise (in some instances), and will eventually be more broadly applicable than iPS cells. Today, gene editing is limited to diseases that have single-gene mutations that give rise only in a subset of adult tissues. That's why most gene editing protocols target blood-cell diseases, like sickle cell anemia or Beta-thalassaemia, because human HSCs can be edited and returned back to the original donor. Gene editing protocols that would fix a disease-causing gene in all the cells of the body (or within multiple tissue and organ systems) would have to be performed at the embryonic stage or soon after and that enters into the grey areas of ethics I've talked about before.

The paper I'd like to highlight today stays away from those murky waters for the time being. Researchers at Stanford isolated HSCs from human patients with sickle cell anemia and used CRISPR to perform gene editing on those cells to replace the mutated version of the beta-globin gene with a corrected version. The new cells were then grown in culture and in mice and expressed the correct version of the gene. This study highlights novel methods to purify 'corrected' stem cells from those cells that weren't successfully edited, so that in theory, a purified population of healthy HSCs could be reintroduced back into the human donor. This a first-step in patient-based, gene-editing therapy that could fix a disease in a particular tissue caused by a single gene (otherwise known as a Mendelian Disease).

There are many hurdles still to get over, but this is proof-of-principle that CRISPR is on the cusp of ushering in a new era of personalized medicine. That of course is how things are progressing in the United States. However, over in China, the wild west of scientific research these days, the first human clinical trials using CRISPR have just started. Clinicians have isolated immune cells from a single patient with lung cancer, induced a genetic mutation in those cells (using CRISPR) to make them more aggressive in fighting that cancer, and put the edited cells back into the patient. This has never been done before and is truly at the frontier of research. No one knows if this will be successful, what the long-term effects will be, or whether the patient will live. It's all unknown and clinical trials in the United States begin sometime in 2017.

Okay, enough about CRISPR and gene editing. But, we're going to keep our feet dipped in the gene pool (har har) for just a few more moments if you'll indulge me.

Many people wonder if our traits, behaviors, and diseases are caused more by genetics or our environment: the old nature vs. nurture argument. I'm a firm believer that our genetics and our environment work in harmony together to influence the way we grow and live with the world. In many cases, genetics holds almost complete sway (e.g. Huntington's Disease, BRCA1/2-related breast cancers, cystic fibrosis) and in other cases our diet, behaviors, and environment are major influencers (e.g. smoking, diet-induced heart disease and diabetes, environmental mutagens and cancer). And for almost everything in life, it's usually a delicate balance between environmental cues and genetic risk.

Last month I discussed how our ancestry influences genetic responses to bacterial infections. This month I want to highlight two studies that also support the nature AND nurture reality of our world. The first paper examined how diet and genetic risk factors contribute to the onset of coronary artery disease (CAD). The researchers found that even among people with 'high risk' for CAD, based only on genetic risk factors, those that adhered to a healthy lifestyle (i.e. non-smoking, no obesity, a healthy diet, and exercising at least once a week) had a 50% less chance of developing CAD. In fact, in every genetic risk category for CAD (low, intermediate, and high), there was a significant decrease in the likelihood of developing CAD for those who had a healthy lifestyle. If that doesn't scream nature AND nurture I don't know what does.

Another interesting paper that I'm still trying to wrap my mind around studied the effects of social status on immune function in monkeys. The researchers found that those monkeys with low social status were more apt to pro-inflammatory immune responses and significantly different total counts of immune cells. Additionally, social status influenced gene-expression patterns in response to challenges to the immune system.

This is an intriguing finding in that it supports the current observations that low socioeconomic status (SES) in human society is correlated with increased risk of disease. (Ahhh, there's that word -correlation.) This paper steps in the direction of finding the mechanisms that actually contribute to the phenomena of low SES and disease, and the primary reason I am highlighting it. We're beginning to move from correlation to direct mechanisms and causation. But we must keep in mind that this study was performed in monkeys, using manipulated social conditions, and it is still a far jump from humans in many regards. So I bring this up so that we are aware that SES most likely directly influences response to disease and this paper identifies the immune system as a major player in this observation (not surprisingly), but more, direct proof is still needed in humans.

Switching gears, two papers this month are pushing ideas from science fiction into the real world. Researchers implanted electrodes into the brains of primates that stimulated leg movement and allowed weight-bearing and walking after by-passing the spinal cord. This interface worked in both healthy primates and those with spinal-cord injuries and a paralyzed leg. The stimulation allowed the paralyzed monkeys to walk (without training) and this technique will eventually be used in humans with spinal cord injuries. The second paper uses a similar technique to establish an interface to help a patient with ALS communicate more effectively with caregivers.

This type of research is phenomenal and brings hope to many paralyzed individuals. The intersection between computers, biology, and neuroscience is going to pioneer some amazing discoveries in the future and I can't wait to see it!

Last of all, I thought I'd highlight a very cool and odd-ball paper (at least for me as a geneticist). To preface, I must say I am not a fan of Donald Trump (no surprise there). After the election I tried as hard as I could to be silent about the results but as friends on Facebook know, I've posted and commented here and there. Trump's pick to lead the Environmental Protection Agency is questionable at the very best and the nomination of Tom Price to lead the Department of Health and Human Services, which the NIH and my work falls under, also has a few causes of concern.

Trump has yet to nominate a candidate for Secretary of the Department of Energy, but if it isn't some oil or gas tycoon I'd be shocked. That's important for a few reasons, particularly for climate change and green energy research. Earlier this month Science published a report which detailed a new method to synthetically create complex organic compounds using carbon dioxide as a carbon source. This is akin to photosynthesis in plants and is a large step in the direction of synthetic photosynthesis in the laboratory - a process still only partially understood. This finding is a big breakthrough for engineering new technologies that may one day be used to grow new plants or scrub our atmosphere of green house gases. The potential is enormous for engineering, energy, healthcare, climate change, and growing our economy. (These results here need to be improved upon, expanded, and replicated...but it's a wonderful development.)

I highlight this because this study was funded by the Department of Energy and is the exact type of cutting-edge science that could be tossed out by the Trump Administration in their purge to get rid of all climate change funding. Even though this research has climate implications, the usefulness of this technology for so many other fields and our economy means that this work is both incredibly important to push forward AND protect from budge cuts. Whether or not you believe in climate change (and you really should take a hard look at the evidence, because climate change IS happening whether or not you want to believe it), this type of research can be caught in the crosshairs of an Administration that clearly isn't interested in facts and could seriously harm America's potential in technology development.

There's a war on science brewing in this country. Discussing these issues may help protect some of this important work, regardless of who is running the show. In the coming months, I plan on writing about some important topics in science in a new series of posts (in addition to my monthly research updates). I'll be posting about hot topics including vaccination (which Trump has been wishy-washy on, unfortunately), the reproducibility crisis in science, and we'll discuss how and why it is so important to be able to differentiate pseudoscience from real science.

Thanks for reading! Have a Merry Christmas and Happy New Year!

Friday, October 28, 2016

October SciDay Friday!

It's the last Friday in October, which means a new science post, continued attempts at walking through leaves, preparing for the coming onslaught of Christmas advertising, and the Cubs waiting for next ye......wait a minute...what's that?.....yep....WORLD SERIES AT WRIGLEY FIELD! I can't believe the Cubs are still playing baseball this late into the year AND for all the marbles. It's a strange feeling typing that particular combination of letters. 

Today I'm going to highlight some interesting papers as always, but there are a few societal issues I want to reexamine and discuss as well. So we'll go from aging and gene expression, to health disparities, sprinkle in some marijuana to get us in the spirit of inebriated debate, and then back to the social implications of CRISPR technology and gene editing that I've touched on before.

First the papers!

It's a challenge to boil down a month's worth of research into a few concise points and this week I've been struggling with what to talk about. But considering I work at the National Institute on Aging, I guess I can always dip back into the comfortable realm of the topics I am surrounded by the most to help me find something to talk about*.

*Disclaimer: Although I work for the National Institutes of Health, the opinions expressed in this post and all others before and after on my websites are my own and not the official representation of the United States government.* (Yes, I've had to include this statement in previous scientific talks and I felt it best to just put that out there right now, particularly for things I'll bring up at the end. I've also realized that many of the articles I link in my posts are often behind a pay wall. I understand if this causes frustration and if you can't access a particular article you can always email any scientist that you may know and they will be happy to oblige you with said the spirit of scientific education, collaboration, and public discourse. [Cough])

It's long been known that as humans age our tissues and bodily functions begin to degenerate. Researchers in the UK and the Netherlands studied the rate at which DNA mutations accumulate in adult stem cells (ASCs) that were isolated from study participants and grown in tissue culture. ASCs are different from embryonic or pluripotent stem cells, which can divide and turn into almost any tissue in the body. Instead, ASCs belong to one type of tissue, such as the liver, or heart, or brain, and they stimulate new cell growth and generate 'younger' cells for that particular tissue. Often this is to replace the older cells that are being turned over. The study confirmed that as we age, all the stem cells in our tissues also age and accumulate random DNA mutations as they replicate their DNA and divide. These seemingly random mutations can lead to predisposition to age-related diseases, like cancer. 

The exciting finding is that although the ASCs from different tissues tend to accumulate DNA mutations at the same rate, the locations of theses mutations in the genome is very tissue-dependent and perhaps not random. This hints at the prospect that some tissues may have better ways of protecting their DNA from disease-causing mutations than others. Although the full mechanism of why this occurs in some tissues and not others has yet to be figured out, it's a promising lead on refining our understanding of age-related disease. 

The next study, conducted at the Albert Einstein College of Medicine in New York, examined whether improvements in health and technology in the last two decades have increased the maximum lifespan of human beings: currently set around 122 years of age. They reported that there appears to be a fixed, upper-limit to increasing the human lifespan and we may never push beyond 120-125 years old. It also appears this boundary is largely influenced by genetics. That's not to say some new technology or gene editing technique in the future may not push this barrier higher (we'll touch on this below), but as of right now nothing current is believed to have expanded human life span to 150-200 years. 

As someone who studies aging, I'm not surprised by this result. It is an awfully difficult thing to protect multiple systems of the body from failing as we get older. Human aging is at the intersection of genetics and the environment (such as drug intervention, diet, sheer luck) and until the genetics are fully understood, it will be difficult to get past 130 years or so, in my opinion. I will go out on a limb and say that perhaps one or two people will push 140 in our lifetimes, but I'm not convinced they would be anything but bed or chair bound (although I hope not because that sounds miserable.) 

Another paper I'd like to highlight came out in Cell late last week. Cell is a great journal, although it can be a little data-heavy and at times the basic science presented can be hard to extrapolate to public health. However, the journal has pushed hard to be innovative and now every paper has a graphical abstract - a visual diagram or picture summarizing the paper's findings in addition to the traditional written abstract. I find the graphical abstract of many papers to be the best part, particularly for scientific work I don't understand at all. I'd like to see more journals adopt this change. Anyways, back to my main point, researchers in the US and Canada discovered that genetic ancestry and natural selection plays a role in how immune cells respond to pathogens. We've long known that different ethnic populations are susceptible to certain diseases and we coming to understand that genetic background can influence how a disease can progress given an individual's ancestry. 

This study provides strong evidence for this on a genetic and molecular level. The authors found that immune cells isolated from European Americans or African Americans each have a unique subset of genes that are expressed in response to the same environmental pathogen. Another important finding is that a large portion of these genetic responses were selected for by local adaption/evolutionary events in our history as a species. This means that local environments, for any given population, naturally selected for particular immune responses to infections and this may contribute to why, today, some populations are more at risk for certain diseases. 

This has enormous implications for our own understanding of healthcare, disease response, and current human evolution. It also underscores the need to continue to push for basic and translational research in underrepresented populations in scientific studies; including women, African Americans, indigenous populations, Africans, Latin and South Americans, Asians....pretty much everyone that's not a Caucasian male, who have been the dominant demographic in a large majority of studies from the late 1800's to late 1900's in the United States. This type of work is so important to truly understand how disease affects each individual and may ultimately help clinicians and scientists better understand disease prevention and progression. It will ideally be a cornerstone of the Precision Medicine Initiative  and will certainly be useful to solve some of the huge disparities in health that affect many Americans in our country. I'll use this as an opportunity to promote my own research, which was just published this week in the journal Scientific Reports. Our laboratory found a profound difference in gene expression in immune cells when comparing African American and white women who have hypertension. Our results suggest that inflammatory diseases, like hypertension, have a racial context to them that need to be further examined to develop better drugs and preventative measures. 

I'm going to pivot gears very quickly and just point out that the crystal structure, aka the shape, size, and conformation, of the human cannabinoid receptor CB1 has been solved. CB1 is the protein target of THC, the chemical in the marijuana plant that gets you stoned....and trippy...and dude, what are we talking about it? Oh yeah, pot! Solving the protein structure of THC's receptor will have important implications for designing new drugs that can induce the same health benefits of marijuana (yes, there are some) without the need to smoke a joint and get high. Crystal structures offer insight into how molecules interact and give scientists a more precise target to develop new drugs. I'm excited to see if any new breakthroughs in medication are tied to this discovery, particularly for mental health issues. 

And now that we're ready to tackle some more 'heady' issues, here's a few social dilemmas to chew on to cure your case of the munchies. Earlier this year I wrote at length about geneticist Dr. George Church's desire to synthesize an entire human genome in the test tube. As a quick recap, we now have the technology to artificially generate most of the human genome in the laboratory, and the Genome Project-Write was put forth as the scientifically-led initiative to get this done. Dr. Church had an interview this week with the Journal of the American Medical Association (JAMA) where he detailed out his ambitious plan to synthesize the human genome for scientific study, all in the hopes of identifying new mechanisms for disease control and prevention, organ transplantation, and other noble health endeavors. This is all fine and good, but I still have some problems with this technology, particularly the fact that we still don't completely understand the ethical ramifications of synthesizing our own human genome. The lack of transparency on aspects of this project are also concerning. Dr. Church attempted to address this issue in his interview:

"JAMA: Your paper in Science stressed responsible innovation. So how does your group plan to move forward responsibly?

Dr. Church: One of the things that we have done already is that most of our new technologies are accompanied by papers on policy, ethics, social, and legal aspects. Another thing is doing it very openly, transparently. So, for example, the meeting [at Harvard in May] that received some attention on this was videotaped and that’s publicly available. The consensus view of the organizers and many of the participants is represented in [the Science paper published in June] that’s publicly available. I think that level of transparency is critical. Also, looking out for any safety and efficacy issues, making sure there’s a dialogue with the FDA on anything that’s intended for diagnostic or therapeutic components."  

I find this a little laughable, only because he fails to mention that the very 'first' meeting about this project was in May 2016 and that was done behind closed doors without invitation to the public or the press. Sure, the videos are available now about the meeting, but the hand-waving and reasoning for secrecy about this meeting is about as solid as Trump's defense on not releasing his taxes. And I put first in quotes because if you read the article announcing this initiative that Dr. Church references, this topic stemmed from talks at a meeting way back last year in October 2015...with little public discussion or input then as well. You're not starting off on the right foot if the very first two meetings aren't widely publicized or available for public discourse. 

Now, I'm not saying Dr. Church or anyone involved with this project has nefarious ideas in mind. Far from it. But this interview is the perfect example of the cognitive dissonance that many scientists share (and many politicians), in that the scientific enterprise must ALWAYS be done in the public eyes, especially when using public funds, and starting off a major initiative like this with closed meetings is not even living up to the standards the project's leaders are advertising. It's very frustrating and an example of science that has lost touch with the public. 

I brought this topic up again for another, more important reason. Last week I was in Vancouver (amazing city with wonderful people) for the annual meeting of the American Society of Human Genetics. Several of the panels and platform sessions discussed the role of genetics in future healthcare. One session focused on the impact of gene editing (using CRISPR technology) in society and its role in healthcare and disease prevention in newborns. I'd estimate there was an audience of at least 400-500 people, many of them geneticists, and several of them asked questions to the speakers and moderators concerning the ethics of modifying our own genomes. 

Questions such as:

-If we use CRISPR technology to increase human lifespan, what is the impact on the climate? On our natural resources? On healthy aging?

-If we use CRISPR to 'fix' polymorphisms that confer disease risk in a newborn, does that mean all babies would need to be first created in vitro?

-How can we use this technology if we still don't understand the implications on a generational level? 

-Won't only the wealthy be able to afford this type of gene therapy? 

-How can we help adults who are already sick?

But perhaps the most important question was asked by a transgendered scientist named Emily, who asked: What is to stop people from using this technology to allow parents to change the race or sexuality identity of their unborn child? What do we do then? 

If you just thought of the movie GATTACA, you aren't alone. It's such a tough question, weighing so many different factors that I can't even begin to scratch at the surface. I'm so glad Emily asked that question and it stumped the moderators. I bring this up here and now because in the same interview between JAMA and Dr. Church, he mentions this:

"JAMA: What’s the difference between a gene editing tool like CRISPR-Cas9 and the type of genome-scale engineering that you’re proposing?

Dr. Church: With editing you might change 1 base pair in a genome—like 1 character in a book. With synthesis you might need to make a whole new edition of a book, where you’d have to make many changes to fix many genes. If you want to make 100 edits with CRISPR, it might be more cost-effective to bring in a few thousand base pairs of DNA that include those 100 edits as 1 big chunk and then essentially do 1 edit that accomplishes 100 things at once. If you wanted to change all triplet codons for all of the genes, for example, that would be very hard to do by editing in the conventional sense, where you change 1 at a time. You might have to make 10 000 to a million changes. It might be easier just to synthesize that and pop it in as 1 edit."

What Dr. Church is suggesting is synthesizing an artificial human genome that now even skips the need to edit using CRISPR, instead just building and designing the thing with as many base changes as one would want, anywhere in the genome. It's an incredible the playing with fire/flying too close to the Sun kind of way. Imagine 'fixing' every cancer-predisposing polymorphism in the human body...or every polymorphism known to be associated with increased lifespan and healthy living. It's a noble idea. However, some of these known locations in the genome are only associated with a given outcome and disease. There is no proof yet they are a driver gene for a particular process. We also don't yet understand what effect all of these changes at one time would have. Remember, our human genome was refined throughout human evolution to be what it is today. Changing everything at one could have disastrous, unforeseen consequences. You can see what I am inferring to here - what does this imply for Emily's question on gender, race, and sexuality in society?

These are all very hard things to grasp and think about but these questions have to be addressed before moving forward in any substantial way. What makes me happy is that a lot of people are starting to ask these questions and at other major scientific meetings. In fact, the programing for the annual meeting for the American Association for the Advancement of Science (AAAS) next February is riddled with talks about gene editing, with some heavy hitters in the field including Emmanuelle Charpentier, George Church, and Alan Leshner. I wish I could go to see what some of them have to say. 

So there you go, a little something to think about today. That's it for October, now go enjoy what's left of your buzz and have a great weekend. GO CUBBIES!